A combined DHA-rich fish oil and cocoa flavanols intervention does not improve cognition or brain structure in older adults with memory complaints: results from the CANN randomized, controlled parallel-design study.

BACKGROUND: There is evidence that both omega-3 long-chain polyunsaturated fatty acids (PUFAs) (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) and cocoa flavanols can improve cognitive performance in both healthy individuals and in those with memory complaints. However, their combined effect is unknown. OBJECTIVES: To investigate the combined effect of EPA/DHA and cocoa flavanols (OM3FLAV) on cognitive performance and brain structures in older adults with memory complaints. METHODS: A randomized placebo-controlled trial of DHA-rich fish oil (providing 1.1 g/d DHA and 0.4 g/d EPA) and a flavanol-rich dark chocolate (providing 500 mg/d flavan-3-ols) was conducted in 259 older adults with either subjective cognitive impairment or mild cognitive impairment. Participants underwent assessment at baseline, 3 mo, and 12 mo. The primary outcome was the number of false-positives on a picture recognition task from the Cognitive Drug Research computerized assessment battery. Secondary outcomes included other cognition and mood outcomes, plasma lipids, brain-derived neurotrophic factor (BDNF), and glucose levels. A subset of 110 participants underwent structural neuroimaging at baseline and at 12 mo. RESULTS: 197 participants completed the study. The combined intervention had no significant effect on any cognitive outcomes, with the exception of reaction time variability (P = 0.007), alertness (P < 0.001), and executive function (P < 0.001), with a decline in function observed in the OM3FLAV group (118.6 [SD 25.3] at baseline versus 113.3 [SD 25.4] at 12 mo for executive function) relative to the control, and an associated decrease in cortical volume (P = 0.039). Compared with the control group, OM3FLAV increased plasma HDL, total cholesterol ratio (P < 0.001), and glucose (P = 0.008) and reduced TG concentrations (P < 0.001) by 3 mo, which were sustained to 12 mo, with no effect on BDNF. Changes in plasma EPA and DHA and urinary flavonoid metabolite concentrations confirmed compliance to the intervention. CONCLUSIONS: These results suggest that cosupplementation with ω-3 PUFAs and cocoa flavanols for 12 mo does not improve cognitive outcomes in those with cognitive impairment. This trial was registered at clinicaltrials.gov as NCT02525198.

APOE ε4 alters associations between docosahexaenoic acid and preclinical markers of Alzheimer's disease.

Docosahexaenoic acid is the main long-chain omega-3 polyunsaturated fatty acids in the brain and accounts for 30-40% of fatty acids in the grey matter of the human cortex. Although the influence of docosahexaenoic acid on memory function is widely researched, its association with brain volumes is under investigated and its association with spatial navigation is virtually unknown. This is despite the fact that spatial navigation deficits are a new cognitive fingerprint for symptomatic and asymptomatic Alzheimer's disease. We investigated the cross-sectional relationship between docosahexaenoic acid levels and the major structural and cognitive markers of preclinical Alzheimer's disease, namely hippocampal volume, entorhinal volume and spatial navigation ability. Fifty-three cognitively normal adults underwent volumetric magnetic resonance imaging, measurements of serum docosahexaenoic acid (DHA, including lysophosphatidylcholine DHA) and APOE ε4 genotyping. Relative regional brain volumes were calculated and linear regression models were fitted to examine DHA associations with brain volume. APOE genotype modulated serum DHA associations with entorhinal cortex volume and hippocampal volume. Linear models showed that greater serum DHA was associated with increased entorhinal cortex volume, but not hippocampal volume, in non APOΕ Îµ4 carriers. APOE also interacted with serum lysophosphatidylcholine DHA to predict hippocampal volume. After testing interactions between DHA and APOE on brain volume, we investigated whether DHA and APOE interact to predict spatial navigation performance on a novel virtual reality diagnostic test for Alzheimer's disease in an independent population of APOE genotyped adults (n = 46). APOE genotype modulated DHA associations with spatial navigation performance, showing that DHA was inversely associated with path integration in APOE ε4 carriers only. This exploratory analysis suggests that interventions aiming to increase DHA blood levels to protect against cognitive decline should consider APOE ε4 carrier status. Future work should focus on replicating our initial findings and establishing whether a specific dose of supplementary DHA, at a particular time in the preclinical disease course can have a positive impact on Alzheimer's disease progression in APOE ε4 carriers.

Changing from a Western to a Mediterranean-style diet does not affect iron or selenium status: results of the New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE) 1-year randomized clinical trial in elderly Europeans.

BACKGROUND: Mediterranean diets limit red meat consumption and increase intakes of high-phytate foods, a combination that could reduce iron status. Conversely, higher intakes of fish, a good source of selenium, could increase selenium status. OBJECTIVES: A 1-y randomized controlled trial [New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe (NU-AGE)] was carried out in older Europeans to investigate the effects of consuming a Mediterranean-style diet on indices of inflammation and changes in nutritional status. METHODS: Selenium and iron intakes and status biomarkers were measured at baseline and after 1 y in 1294 people aged 65-79 y from 5 European countries (France, Italy, the Netherlands, Poland, and the United Kingdom) who had been randomly allocated either to a Mediterranean-style diet or to remain on their habitual, Western diet. RESULTS: Estimated selenium intakes increased significantly with the intervention group (P < 0.01), but were not accompanied by changes in serum selenium concentrations. Iron intakes also increased (P < 0.001), but there was no change in iron status. However, when stratified by study center, there were positive effects of the intervention on iron status for serum ferritin for participants in Italy (P = 0.04) and France (P = 0.04) and on soluble transferrin receptor (sTfR) for participants in Poland (P < 0.01). Meat intake decreased and fish intake increased to a greater degree in the intervention group, relative to the controls (P < 0.01 for both), but the overall effects of the intervention on meat and fish intakes were mainly driven by data from Poland and France. Changes in serum selenium in the intervention group were associated with greater changes in serum ferritin (P = 0.01) and body iron (P = 0.01), but not sTfR (P = 0.73); there were no study center × selenium status interactions for the iron biomarkers. CONCLUSIONS: Consuming a Mediterranean-style diet for 1 y had no overall effect on iron or selenium status, although there were positive effects on biomarkers of iron status in some countries. The NU-AGE trial was registered at clinicaltrials.gov as NCT01754012.

Changes in Dietary Intake and Adherence to the NU-AGE Diet Following a One-Year Dietary Intervention among European Older Adults-Results of the NU-AGE Randomized Trial.

BACKGROUND: The Mediterranean Diet has been proposed as an effective strategy to reduce inflammaging, a chronic low grade inflammatory status, and thus, to slow down the aging process. We evaluated whether a Mediterranean-like dietary pattern specifically targeting dietary recommendations of people aged over 65 years (NU-AGE diet) could be effective to shift dietary intake of older adults towards a healthful diet. METHODS: Adults aged 65⁻80 years across five EU-centers were randomly assigned to a NU-AGE diet group or control group. The diet group followed one year of NU-AGE dietary intervention specifying consumption of 15 food groups plus the use of a vitamin D supplement. Participants in the diet group received counselling and individually tailored dietary advice, food products and a vitamin D supplement. Dietary intake was assessed by means of seven-day food records at baseline and one-year follow-up. A continuous NU-AGE index (0⁻160 points) was developed to assess NU-AGE diet adherence. RESULTS: In total 1296 participants were randomized and 1141 participants completed the intervention (571 intervention, 570 control). After one year, the diet group improved mean intake of 13 out of 16 NU-AGE dietary components (p < 0.05), with a significant increase in total NU-AGE index (difference in mean change = 21.3 ± 15.9 points, p < 0.01). CONCLUSIONS: The NU-AGE dietary intervention, based on dietary recommendations for older adults, consisting of individual dietary counselling, free healthy foods and a vitamin D supplement, may be a feasible strategy to improve dietary intake in an aging European population.

Cross-Sectional Analysis of the Correlation Between Daily Nutrient Intake Assessed by 7-Day Food Records and Biomarkers of Dietary Intake Among Participants of the NU-AGE Study.

Methods for measuring diet composition and quantifying nutrient intake with sufficient validity are essential to study the association between nutrition and health outcomes and risk of diseases. 7-day food records provides a quantification of food actually and currently consumed and is interesting for its use in intervention studies to monitor diet in a short-term period and to guide participants toward changing their intakes. The objective of this study is to analyze the correlation/association between the daily intake of selected nutrients (collected by a 7-day food records plus a mineral/vitamin supplementation questionnaire) and estimates of energy expenditure as well as blood and urine biomarkers of dietary intakes in 1,140 healthy elderly subjects (65-79 years) at baseline of the NU-AGE intervention study (NCT01754012, clinicaltrials.gov). The results show that: the daily intake of energy correlated significantly with predicted total energy expenditure (pTEE) (ρ = 0.459, p < 0.001, and q < 0.001); protein intake correlated significantly with the ratio of 24 h urinary urea to creatinine excretion (ρ = 0.143 for total protein intake, ρ = 0.296 for animal protein intake, and ρ = 0.359 for protein intake/body weight, p < 0.001 and q < 0.001 for each correlation); vitamin B12 and folate intakes correlated significantly with their serum concentrations (ρ = 0.151 and ρ = 0.363, respectively; p < 0.001 and q < 0.001 for each correlation); sodium and potassium intakes correlated significantly with their 24 h urinary excretion (ρ = 0.298 and ρ = 0.123, respectively; p < 0.001 and q < 0.001 for each correlation); vitamin B12 and folate intakes were negatively associated with plasma homocysteine measure (p = 0.001 and p = 0.004, respectively); stratifying subjects by gender, the correlations between energy intake and pTEE and between potassium intake and its 24 h urinary excretion lost their significance in women. Even if the plasma and urinary levels of these nutrients depend on several factors, the significant correlations between daily reported intake of nutrients (protein, vitamin B12, folate, and sodium) and their blood/urinary markers confirmed that the 7-day food records (plus a supplementation questionnaire) provides reliable data to evaluate short-term current dietary intake in European elderly subjects and it can be exploited to guide and monitor NU-AGE participants through the shift of their diet according NU-AGE recommendations.

One-Year Consumption of a Mediterranean-Like Dietary Pattern With Vitamin D3 Supplements Induced Small Scale but Extensive Changes of Immune Cell Phenotype, Co-receptor Expression and Innate Immune Responses in Healthy Elderly Subjects: Results From the United Kingdom Arm of the NU-AGE Trial.

Amongst the major features of aging are chronic low grade inflammation and a decline in immune function. The Mediterranean diet (MedDiet) is considered to be a valuable tool to improve health status, and although beneficial effects have been reported, to date, immunological outcomes have not been extensively studied. We aimed to test the hypothesis that 1 year of a tailored intervention based on the MedDiet with vitamin D (10 µg/day) would improve innate immune responses in healthy elderly subjects (65-79 years) from the English cohort (272 subjects recruited) of the NU-AGE randomized, controlled study (clinicaltrials.gov, NCT01754012). Of the 272 subjects forming the United Kingdom cohort a subgroup of 122 subjects (61 in the intervention group and 61 in the control group) was used to evaluate ex vivo innate immune response, phenotype of circulating immune cells, and levels of pro- and anti-inflammatory markers. Odds Ratio (OR) was calculated for all the parameters analyzed. After adjustment by gender, MedDiet-females with a BMI < 31 kg/m2 had a significant upregulation of circulating CD40+CD86+ cells (OR 3.44, 95% CI 1.01-11.75, P = 0.0437). Furthermore, in all MedDiet subjects, regardless of gender, we observed a MedDiet-dependent changes, although not statistically significant of immune-critical parameters including T cell degranulation, cytokine production and co-receptor expression. Overall, our study showed that adherence to an individually tailored Mediterranean-like dietary pattern with a daily low dose of vitamin D3 supplements for 1 year modified a large variety of parameters of immune function in healthy, elderly subjects. We interpreted these data as showing that the MedDiet in later life could improve aspects of innate immunity and thus it could aid the design of strategies to counteract age-associated disturbances. Clinical Trial Registration: clinicaltrials.gov, NCT01754012.

A Mediterranean-like dietary pattern with vitamin D3 (10 µg/d) supplements reduced the rate of bone loss in older Europeans with osteoporosis at baseline: results of a 1-y randomized controlled trial.

Background: The Mediterranean diet (MD) is widely recommended for the prevention of chronic disease, but evidence for a beneficial effect on bone health is lacking. Objective: The aim of this study was to examine the effect of a Mediterranean-like dietary pattern [NU-AGE (New Dietary Strategies Addressing the Specific Needs of the Elderly Population for Healthy Aging in Europe)] on indexes of inflammation with a number of secondary endpoints, including bone mineral density (BMD) and biomarkers of bone and collagen degradation in a 1-y multicenter randomized controlled trial (RCT; NU-AGE) in elderly Europeans. Design: An RCT was undertaken across 5 European centers. Subjects in the intervention group consumed the NU-AGE diet for 1 y by receiving individually tailored dietary advice, coupled with supplies of foods including whole-grain pasta, olive oil, and a vitamin D3 supplement (10 µg/d). Participants in the control group were provided with leaflets on healthy eating available in their country. Results: A total of 1294 participants (mean ± SD age: 70.9 ±4.0 y; 44% male) were recruited to the study and 1142 completed the 1-y trial. The Mediterranean-like dietary pattern had no effect on BMD (site-specific or whole-body); the inclusion of compliance to the intervention in the statistical model did not change the findings. There was also no effect of the intervention on the urinary biomarkers free pyridinoline or free deoxypyridinoline. Serum 25-hydroxyvitamin D significantly increased and parathyroid hormone decreased (P < 0.001) in the MD compared with the control group. Subgroup analysis of individuals with osteoporosis at baseline (site-specific BMD T-score ≤ -2.5 SDs) showed that the MD attenuated the expected decline in femoral neck BMD (n = 24 and 30 in MD and control groups, respectively; P = 0.04) but had no effect on lumbar spine or whole-body BMD. Conclusions: A 1-y intervention of the Mediterranean-like diet together with vitamin D3 supplements (10 µg/d) had no effect on BMD in the normal age-related range, but it significantly reduced the rate of loss of bone at the femoral neck in individuals with osteoporosis. The NU-AGE trial is registered at clinicaltrials.gov as NCT01754012.

Iron status in the elderly.

Iron deficiency anaemia is prevalent in older age, particularly after the age of 80. Serum ferritin concentrations also decline, although there is no evidence to suggest that changes in iron stores are an inevitable consequence of ageing. Chronic inflammation is a common condition in older people, making the measurement of iron status difficult, and it is likely that elevated levels of circulating hepcidin are responsible for changes in iron metabolism that result in systemic iron depletion. Other contributory factors are poor diet and some medications, such as aspirin. Anaemia in older age has undesirable health outcomes, including increased susceptibility to falling and depression. However, there are concerns about possible adverse effects of iron supplements, either in relation to pro-inflammatory effects in the gut or inappropriate tissue iron deposition. Brain iron levels are increased with age-related degenerative diseases, but it is not known if this is the cause or a consequence of the disease, and genetic factors are likely to play a role. In order to maintain body iron within the normal range a personalised approach is required, taking into account all of the factors that may affect iron metabolism and the available strategies for preventing iron deficiency or overload.